Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells.
EBV-induced gene 3 (EBI-3) codes for a soluble type I receptor homologous to the p40 subunit of IL-12 that is expressed by APCs following activation. In this study, we assessed the role of EBI-3 in a model of lung melanoma metastasis. Intravenous injection of the B16-F10 cell line resulted in a significant reduction of lung tumor metastasis in EBI-3(-/-) recipient mice compared with wild-type mice. The immunological finding accompanying this effect was the expansion of a newly described cell subset called IFN-gamma producing killer dendritic cells associated with CD8(+) T cell responses in the lung of EBI-3(-/-) mice including IFN-gamma release and TNF-alpha-induced programmed tumor cell death. Depletion of CD8(+) T cells as well as targeting T-bet abrogated the protective effects of EBI-3 deficiency on lung melanoma metastases. Finally, adoptive transfer of EBI-3(-/-) CD8(+) T cells into tumor bearing wild-type mice inhibited lung metastasis in recipient mice. Taken together, these data demonstrate that targeting EBI-3 leads to a T-bet-mediated antitumor CD8(+) T cell responses in the lung.
Sauer
Kerstin A
KA
Laboratory of Cellular and Molecular Immunology of the Lung, I. Medical Clinic, University of Mainz, Germany.
Maxeiner
Joachim H
JH
Karwot
Roman
R
Scholtes
Petra
P
Lehr
Hans A
HA
Birkenbach
Mark
M
Blumberg
Richard S
RS
Finotto
Susetta
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D055786:Gene Knockout Techniques; D007157:Immunologic Surveillance / Q000235:genetics; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D009368:Neoplasm Transplantation; D018121:Receptors, Cytokine / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000098815:T-bet Transcription Factor
C499601:Ebi3 protein, mouse; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor